This proposal seeks continued support to study the structural basis of specific protein-nucleic acid interactions at the molecular level. The lines of attack will be (1) Crystallographic study of tRNA and tRNA-ligase complexes; specifically, to complete the 4 angstrom units study of yeast tRNA Met and to survey crystallization conditions and then initiate studies on suitable specimens of Class III tRNAs and a variety of tRNA-ligase complexes. (2) NMR studies (either C13 or H1) of the chemical environment and motional parameters of tRNA in various states using enzymatically inserted site specific probes. (3) Photo-induced crosslinking of tRNA and its cognate proteins to map the contact sites both on the tRNA structure as well as the protein; specifically, to complete the analysis of the interaction of the E. coli methionine-tRNA ligase and active tryptic fragment with four substrate tRNAs.